Cell membranes are not merely passive barriers to diffusion, for they contain enzymes, specific receptors and transport systems. Full understanding of many biologically important processes requires detailed knowledge of these membrane functions. One area in which information is sparse is the specific interaction of transport proteins with cell membranes to effect the entry of a small molecule. Examples of such transport systems are: transcobalamin II-vitamin B12, transferrin-iron, and hemopexin-heme. These systems have essential functions; aberrations in these processes can be deleterious; and rational clinical treatment of states, such as certain vitamin deficiencies and abnormal hormone responses, requires an understanding of the mechanisms of action of the transport proteins. Hemopexin, a serum beta-glycoprotein, functions in the selective transport of intravascular heme to the liver and thus plays a role in conserving iron as well as in preventing toxic effects of heme. The heme-hemopexin-liver cell system should be an informative model of transport protein-ligand-cell interactions because of the specificity of the interaction of hemopexin with the liver, the information available on the chemistry and biology of hemopexin, and its analogy with other protein-mediated transport processes. Hemopexin's function will be studied in several ways. First, the interaction of heme-hemopexin with the liver in vivo and liver cells and liver cell membranes in vitro will continue to be characterized. Questions of interest include: How does the heme-hemopexin complex interact with the hepatocyte? Does the complex enter the liver as a unit or does hemopexin recycle? What is the species specificity, stoichiometry, kinetics and affinity of this interaction? What is the nature of the recognition site on the membrane for the complex? Second, we will study the fate of heme and hemopexin inside the liver cell, with particular emphasis on the role of subcellular organelles like lysosomes and on the intracellular transport of heme to microsomal heme oxygenase.